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1.
J Hematol Oncol ; 6(1): 81, 2013 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-24283202

RESUMO

BACKGROUND: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. METHODS: Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. RESULTS: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. CONCLUSIONS: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts.


Assuntos
Plaquetas/patologia , Mielofibrose Primária/sangue , Mielofibrose Primária/tratamento farmacológico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Janus Quinases/antagonistas & inibidores , Masculino , Nitrilas , Contagem de Plaquetas , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas , Resultado do Tratamento
3.
Lancet ; 371(9610): 395-403, 2008 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-18242413

RESUMO

BACKGROUND: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. METHODS: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30x10(9)/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50x10(9)/L to 200x10(9)/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count > or =50x10(9)/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. FINDINGS: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23.4-52.8], p=0.0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38.7-73.7], p<0.0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0.0001). Patients given romiplostim achieved platelet counts of 50x10(9)/L or more on a mean of 13.8 (SE 0.9) weeks (mean 12.3 [1.2] weeks in splenectomised group vs 15.2 [1.2] weeks in non-splenectomised group) compared with 0.8 (0.4) weeks for those given placebo (0.2 [0.1] weeks vs 1.3 [0.8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. INTERPRETATION: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.


Assuntos
Proteínas de Transporte/uso terapêutico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Receptores Fc/uso terapêutico , Adulto , Idoso , Proteínas de Transporte/administração & dosagem , Proteínas de Transporte/efeitos adversos , Doença Crônica/tratamento farmacológico , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/imunologia , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão , Esplenectomia , Trombopoetina , Resultado do Tratamento
4.
Am Surg ; 70(1): 71-4, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14964553

RESUMO

There are few cases of splenic infarction associated with antiphospholipid antibody reported in the literature. We present two cases of splenic infarction associated with anticardiolipin antibody, one complicated by the development of a splenic pseudocyst. Clinical diagnostic features of splenic infarction are described. In addition, a review of the literature on thrombotic manifestations of antiphospholipid syndrome is presented.


Assuntos
Anticorpos Anticardiolipina/imunologia , Infarto do Baço/imunologia , Adulto , Cistos/complicações , Cistos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esplenectomia , Esplenopatias/complicações , Esplenopatias/cirurgia , Infarto do Baço/complicações , Infarto do Baço/cirurgia
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